Can misfolded proteins be beneficial? The HAMLET case

@article{PetterssonKastberg2009CanMP,
  title={Can misfolded proteins be beneficial? The HAMLET case},
  author={Jenny Pettersson-Kastberg and Sonja Aits and Lotta Gustafsson and Anki Mossberg and Petter Storm and Maria Trulsson and Filip Persson and K. Hun Mok and Catharina Svanborg},
  journal={Annals of Medicine},
  year={2009},
  volume={41},
  pages={162 - 176}
}
By changing the three-dimensional structure, a protein can attain new functions, distinct from those of the native protein. Amyloid-forming proteins are one example, in which conformational change may lead to fibril formation and, in many cases, neurodegenerative disease. We have proposed that partial unfolding provides a mechanism to generate new and useful functional variants from a given polypeptide chain. Here we present HAMLET (Human Alpha-lactalbumin Made LEthal to Tumor cells) as an… 
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HAMLET: functional properties and therapeutic potential.
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Human α-lactalbumin made lethal to tumor cells (HAMLET) is the first member in a new family of protein-lipid complexes that kills tumor cells with high selectivity and limits the progression of human glioblastomas, with no evidence of toxicity for normal brain or bladder tissue.
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The biological activities of protein/oleic acid complexes reside in the fatty acid.
Structure and function of human α‐lactalbumin made lethal to tumor cells (HAMLET)‐type complexes
TLDR
The gain of new, beneficial function upon partial protein unfolding and fatty acid binding is a remarkable phenomenon, and may reflect a significant generic route of functional diversification of proteins via varying their conformational states and associated ligands.
Alternatively folded proteins with unexpected beneficial functions.
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The cellular targets that appear to be strongly correlated with tumour cell death are introduced in the present article.
Lipids as Tumoricidal Components of Human α-Lactalbumin Made Lethal to Tumor Cells (HAMLET)
TLDR
It is shown by natural abundance 13C NMR that the lipid in HAMLET is deprotonated and by chromatography that oleate rather than oleic acid is the relevant HAMLET constituent.
Bioactivity of α-Lactalbumin Related to its Interaction with Fatty Acids: A Review
TLDR
The proposed functions for α-LA open new perspectives for its use as a potential ingredient to be added in functional foods or in nutraceutical products.
Structural and mechanistic insights into the yeast disaggregase Hsp104
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This thesis found that in this state Hsp104 displays an increase in rigidity, which is proposed as a pre-payment of the entropic cost of substrate binding, and developed a comprehensive model for how the Hsp 104 hexamer engages substrate and unleashes its remodeling capabilities.
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